Mitochondrial Akt Signaling Modulated Reprogramming of Somatic Cells

Abstract The signaling mechanisms controlling somatic cell reprogramming are not fully understood. In this study, we report a novel role for mitochondrial Akt1 signaling that enhanced somatic cell reprogramming efficiency. The role of mitochondrial Akt1 in somatic cell reprogramming was investigated...

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Autores principales:	Yu-Han Chen, Ching-Chieh Su, Wu Deng, Leslie F. Lock, Peter J. Donovan, Matthew A. Kayala, Pierre Baldi, Hsiao-Chen Lee, Yumay Chen, Ping H. Wang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7ec40b87572449a09587a27ab8b43b2d
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spelling	oai:doaj.org-article:7ec40b87572449a09587a27ab8b43b2d2021-12-02T15:08:08ZMitochondrial Akt Signaling Modulated Reprogramming of Somatic Cells10.1038/s41598-019-46359-62045-2322https://doaj.org/article/7ec40b87572449a09587a27ab8b43b2d2019-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-46359-6https://doaj.org/toc/2045-2322Abstract The signaling mechanisms controlling somatic cell reprogramming are not fully understood. In this study, we report a novel role for mitochondrial Akt1 signaling that enhanced somatic cell reprogramming efficiency. The role of mitochondrial Akt1 in somatic cell reprogramming was investigated by transducing fibroblasts with the four reprogramming factors (Oct4, Sox2, Klf4, c-Myc) in conjunction with Mito-Akt1, Mito-dnAkt1, or control virus. Mito-Akt1 enhanced reprogramming efficiency whereas Mito-dnAkt1 inhibited reprogramming. The resulting iPSCs formed embryoid bodies in vitro and teratomas in vivo. Moreover, Oct4 and Nanog promoter methylation was reduced in the iPSCs generated in the presence of Mito-Akt1. Akt1 was activated and translocated into mitochondria after growth factor stimulation in embryonic stem cells (ESCs). To study the effect of mitochondrial Akt in ESCs, a mitochondria-targeting constitutively active Akt1 (Mito-Akt1) was expressed in ESCs. Gene expression profiling showed upregulation of genes that promote stem cell proliferation and survival and down-regulation of genes that promote differentiation. Analysis of cellular respiration indicated similar metabolic profile in the resulting iPSCs and ESCs, suggesting comparable bioenergetics. These findings showed that activation of mitochondrial Akt1 signaling was required during somatic cell reprogramming.Yu-Han ChenChing-Chieh SuWu DengLeslie F. LockPeter J. DonovanMatthew A. KayalaPierre BaldiHsiao-Chen LeeYumay ChenPing H. WangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-14 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yu-Han Chen Ching-Chieh Su Wu Deng Leslie F. Lock Peter J. Donovan Matthew A. Kayala Pierre Baldi Hsiao-Chen Lee Yumay Chen Ping H. Wang Mitochondrial Akt Signaling Modulated Reprogramming of Somatic Cells
description	Abstract The signaling mechanisms controlling somatic cell reprogramming are not fully understood. In this study, we report a novel role for mitochondrial Akt1 signaling that enhanced somatic cell reprogramming efficiency. The role of mitochondrial Akt1 in somatic cell reprogramming was investigated by transducing fibroblasts with the four reprogramming factors (Oct4, Sox2, Klf4, c-Myc) in conjunction with Mito-Akt1, Mito-dnAkt1, or control virus. Mito-Akt1 enhanced reprogramming efficiency whereas Mito-dnAkt1 inhibited reprogramming. The resulting iPSCs formed embryoid bodies in vitro and teratomas in vivo. Moreover, Oct4 and Nanog promoter methylation was reduced in the iPSCs generated in the presence of Mito-Akt1. Akt1 was activated and translocated into mitochondria after growth factor stimulation in embryonic stem cells (ESCs). To study the effect of mitochondrial Akt in ESCs, a mitochondria-targeting constitutively active Akt1 (Mito-Akt1) was expressed in ESCs. Gene expression profiling showed upregulation of genes that promote stem cell proliferation and survival and down-regulation of genes that promote differentiation. Analysis of cellular respiration indicated similar metabolic profile in the resulting iPSCs and ESCs, suggesting comparable bioenergetics. These findings showed that activation of mitochondrial Akt1 signaling was required during somatic cell reprogramming.
format	article
author	Yu-Han Chen Ching-Chieh Su Wu Deng Leslie F. Lock Peter J. Donovan Matthew A. Kayala Pierre Baldi Hsiao-Chen Lee Yumay Chen Ping H. Wang
author_facet	Yu-Han Chen Ching-Chieh Su Wu Deng Leslie F. Lock Peter J. Donovan Matthew A. Kayala Pierre Baldi Hsiao-Chen Lee Yumay Chen Ping H. Wang
author_sort	Yu-Han Chen
title	Mitochondrial Akt Signaling Modulated Reprogramming of Somatic Cells
title_short	Mitochondrial Akt Signaling Modulated Reprogramming of Somatic Cells
title_full	Mitochondrial Akt Signaling Modulated Reprogramming of Somatic Cells
title_fullStr	Mitochondrial Akt Signaling Modulated Reprogramming of Somatic Cells
title_full_unstemmed	Mitochondrial Akt Signaling Modulated Reprogramming of Somatic Cells
title_sort	mitochondrial akt signaling modulated reprogramming of somatic cells
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/7ec40b87572449a09587a27ab8b43b2d
work_keys_str_mv	AT yuhanchen mitochondrialaktsignalingmodulatedreprogrammingofsomaticcells AT chingchiehsu mitochondrialaktsignalingmodulatedreprogrammingofsomaticcells AT wudeng mitochondrialaktsignalingmodulatedreprogrammingofsomaticcells AT leslieflock mitochondrialaktsignalingmodulatedreprogrammingofsomaticcells AT peterjdonovan mitochondrialaktsignalingmodulatedreprogrammingofsomaticcells AT matthewakayala mitochondrialaktsignalingmodulatedreprogrammingofsomaticcells AT pierrebaldi mitochondrialaktsignalingmodulatedreprogrammingofsomaticcells AT hsiaochenlee mitochondrialaktsignalingmodulatedreprogrammingofsomaticcells AT yumaychen mitochondrialaktsignalingmodulatedreprogrammingofsomaticcells AT pinghwang mitochondrialaktsignalingmodulatedreprogrammingofsomaticcells
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Mitochondrial Akt Signaling Modulated Reprogramming of Somatic Cells

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